RT Journal Article
SR Electronic
T1 Resolving structural diversity of Carbapenemase-producing gram-negative bacteria using single molecule sequencing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 456897
DO 10.1101/456897
A1 Nicholas Noll
A1 Eric Urich
A1 Daniel Wüthrich
A1 Vladimira Hinic
A1 Adrian Egli
A1 Richard A. Neher
YR 2018
UL http://biorxiv.org/content/early/2018/10/30/456897.abstract
AB Carbapenemase-producing bacteria are resistant against almost all commonly used betalactam and cephalosporin antibiotics and represent a growing public health crisis. Carbapenemases reside predominantly in mobile genetic elements and rapidly spread across genetic backgrounds and species boundaries. Here, we report more than one hundred finished, high quality genomes of carbapenemase producing enterobacteriaceae, P. aeruginosa and A. baumannii sequenced with Oxford Nanopore and Illumina technologies. We developed a number of high-throughput criteria to assess the quality of fully assembled genomes for which curated references do not exist. Using this diverse collection of closed genomes and plasmids, we demonstrate rapid movement of carbapenemase between genomic neighborhoods, sequence types, and across species boundaries with distinct patterns for different carbapenemases. Lastly, we present evidence of multiple ancestral recombination events between different Enterobacteriaceae MLSTs. Taken together, our samples suggest a hierarchical picture of genomic variation produced by the evolution of carbapenemase producing bacteria that will require new models to adequately understand and track.